Description

START (StAR-related lipid-transfer) is a lipid-binding domain in StAR, HD-ZIP and signalling proteins [PMID: 10322415]. StAR (Steroidogenic Acute Regulatory protein) is a mitochondrial protein that is synthesised in response to luteinising hormone stimulation [PMID: 7961770].
Expression of the protein in the absence of hormone stimulation is sufficient to induce
steroid production, suggesting that this protein is required in the acute regulation of
steroidogenesis. Representatives of the START domain family have
been shown to bind different ligands such as sterols (StAR protein) and
phosphatidylcholine (PC-TP). Ligand binding by the START domain can also
regulate the activities of other domains that co-occur with the START domain
in multidomain proteins such as Rho-gap, the homeodomain,
and the thioesterase domain [PMID: 10322415, PMID: 11276083].

The crystal structure of START domain of human MLN64 shows an
alpha/beta fold built around an U-shaped incomplete beta-barrel. Most
importantly, the interior of the protein encompasses a 26 x 12 x 11 Angstroms
hydrophobic tunnel that is apparently large enough to bind a single
cholesterol molecule [PMID: 10802740]. The START domain structure revealed an unexpected
similarity to that of the birch pollen allergen Bet v 1 and to bacterial
polyketide cyclases/aromatases [PMID: 11276083, PMID: 10802740].

This superfamily represents an alpha/beta sandwich structural domain found in a wide variety of protein families, including STAR-related lipid transfer proteins and homeobox-leucine zipper proteins.